The primary objective of the study is to evaluate the proportion of responders (that is, greater than or equal to [>=] 30 percent reduction from Baseline in blood phenylalanine [Phe] level) to treatment with Kuvan® (sapropterin dihydrochloride) 20 milligram per kilogram per day (mg/kg/day) for 28 days.

ENDURE: A Phase IV, Prospective, Open-label, Uncontrolled, Multi-centre Cohort Trial to Assess the Responsiveness of Subjects With Phenylketonuria (PKU) to Treatment With Kuvan® 20 mg/kg/Day for 28 Days

An Adverse Event (AE) is defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to Baseline during a clinical study with an investigational medicinal product (IMP), regardless of causal relationship and even if no IMP has been administered.

Percentage of Early-, Late-, Partial-Responders and Non-responders to Treatment With Kuvan® [ Time Frame: Baseline up to Day 28 +/- 1 ] [ Designated as safety issue: No ]

Early responders defined as percentage of participants with at least 30 percent reduction in Phe levels within the first seven days of treatment. Late responders defined as percentage of participants with less than 30 percent reduction in Phe levels within first seven days of treatment, but at least 30 percent reduction in Phe levels within 28 +/- 1 days of treatment. Partial responders defined as percentage of participants with Phe levels reduction between 10 and 30 percent at any blood measurement within the 28 +/- 1 days of treatment. Non-responders defined as percentage of participants with a Phe level reduction of less than 10 percent within 28 +/- 1 days.

Percentage of Participants With Greater Than or Equal to (>=) 30 Percent, 20 to 30 Percent, 10 to 20 Percent and Less Than (<) 10 Percent Reduction in Blood Phe Levels According to Phenylketonuria (PKU) Phenotypes [ Time Frame: Baseline up to Day 28 +/- 1 ] [ Designated as safety issue: No ]

Percentage of Early-, Late- and Partial-Responders According to Phenotype [ Time Frame: Baseline up to Day 28 +/- 1 ] [ Designated as safety issue: No ]

The PKU is categorized as per phenotype into classical PKU: (blood Phe levels > 1200 mcmol/l), mild PKU (blood Phe levels 600 to 1200 mcmol/l), mild HPA (blood Phe levels 300 to 600 mcmol/l). Early responders defined as percentage of participants with at least 30 percent reduction in Phe levels within the first seven days of treatment. Late responders defined as percentage of participants with less than 30 percent reduction in Phe levels within first seven days of treatment, but at least 30 percent reduction in Phe levels within 28 +/- 1 days of treatment. Partial responders defined as percentage of participants with Phe levels reduction between 10 and 30 percent at any blood measurement within the 28 +/- 1 days of treatment.

Phenylalanine-to-tyrosine ratio is the best indicator of dopamine availability in PKU. The change in blood phenylalanine-to-tyrosine ratio at Day 28 was calculated as blood phenylalanine-to-tyrosine ratio at Day 28 minus blood phenylalanine-to-tyrosine ratio at Baseline.

Female subjects of childbearing potential (and, if appropriate, male subjects with female partners of childbearing potential) must be willing to avoid pregnancy by using an adequate method of contraception (defined as two barrier methods or one barrier method with spermicide, or intrauterine device or use of the oral female contraceptive) for 4 weeks prior to, during and 12 weeks after the last dose of trial medication

Women of childbearing potential (for the purpose of this trial, women of childbearing potential are defined as "All female subjects after puberty unless they are post-menopausal for at least 2 years, are surgically sterile or are sexually inactive") must have a negative urine pregnancy test at the Baseline visit

Exclusion Criteria:

Subjects who have documented BH4 deficiency

Subjects who have any contraindications to receive Kuvan® as outlined in the summary of product characteristics (SmPC) not willing or able to comply with the study procedures

Subjects who are pregnant, planning for pregnancy or breastfeeding

Subjects who have been exposed to any investigational medicinal drugs or treatments within 30 days or 5 half-lives, whichever is longer, prior to the Screening visit

Have any medical condition that, in the judgment of the investigator, would jeopardize the subject's safety following exposure to study drug or would significantly interfere with the subject's ability to comply with the provisions of the protocol

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01082328